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PubMed1990

Detecting isolation by distance using phylogenies of genes.

We introduce a method for analyzing phylogenies of genes sampled from a geographically structured population. A parsimony method can be used to compute s, the minimum number of migration events between pairs of populations sampled, and the value of s can be used to estimate the effective migration rate M, the value of Nm in an island model with local populations of size N and a migration rate m that would yield the same value of s. Extensive simulations show that there is a simple relationship between M and the geographic distance between pairs of samples in one- and two-dimensional models of isolation by distance. Both stepping-stone and lattice models were simulated. If two demes k steps apart are sampled, then, s, the average value of s, is a function only of k/(Nm) in a one-dimensional model and is a function only of k/(Nm)2 in a two-dimensional model. Furthermore, log(M) is approximately a linear function of log(k). In a one-dimensional model, the regression coefficient is approximately -1 and in a two-dimensional model the regression coefficient is approximately -0.5. Using data from several locations, the regression of log(M) on log(distance) may indicate whether there is isolation by distance in a population at equilibrium and may allow an estimate of the effective migration rate between adjacent sampling locations. Alternative methods for analyzing DNA sequence data from a geographically structured population are discussed. An application of our method to the data of R. L. Cann, M. Stoneking and A. C. Wilson on human mitochondrial DNA is presented.

Computer Simulation↗
PubMed1993

Chiasma interference as a function of genetic distance.

For many organisms, meiotic double crossing over is less frequent than expected on the assumption that exchanges occur at random with respect to each other. This "interference," which can be almost total for nearby intervals, diminishes as the intervals in which the double crossovers are scored are moved farther apart. Most models for interference have assumed, at least implicitly, that the intensity of interference depends inversely on the physical distance separating the intervals. However, several observations suggest that interference depends on genetic distance (Morgans) rather than physical distance (base pairs or micrometers). Accordingly, we devise a model in which interference is related directly to genetic distance. Its central feature is that recombinational intermediates (C's) have two fates--they can be resolved with crossing over (Cx) or without (Co). We suppose that C's are distributed at random with respect to each other (no interference); interference results from constraints on the resolution of C's. The basic constraint is that each pair of neighboring Cx's must have between them a certain number of Co's. The required number of intervening Co's for a given organism or chromosome is estimated from the fraction of gene conversions that are unaccompanied by crossover of flanking markers. The predictions of the model are compared with data from Drosophila and Neurospora.

Animals↗
PubMed1995

Spatial structure of two-locus genotypes under isolation by distance.

Extensive Monte Carlo simulations are conducted of spatial distributions of two-locus genotypes in large, continuous populations under isolation by distance models. The results show that substantial patches of double homozygotes are present in the spatial structures, even when loci are unlinked. The stochastic spread of identical two-locus genotypes largely outpowers the tendency for recombination to decouple patterns for separate loci. A spatial patch is a large area containing mostly one double homozygous genotype in a highly contiguous constellation. This patch structure is reflected in high positive spatial autocorrelations and large excesses of pairs, or joins, of identical double homozygotes at short-to-intermediate distances of spatial separation. Although spatial patches of double homozygotes are the dominant spatial feature, and the major contributors to overall high levels of autocorrelations among two-locus genotypes, other substantial features include areas of concentrations of identical genotypes heterozygous at only one locus. One implication of the patch structure is the presence of high levels of linkage disequilibrium, caused by isolation by distance even for unlinked loci, at some spatial scales; yet the disequilibrium in the large total populations is near 0. Thus linkage disequilibrium produced by isolation by distance is highly dependent on spatial scale. Another implication is that high degrees of spatial structuring and autocorrelations are produced for genetic variation controlling quantitative traits, at least when the number of loci is relatively small, under a wide range of situations, even if the trait is selectively neutral. The significance of the results to field studies is also examined.

Diploidy↗
PubMed1997

Genetic differentiation and estimation of gene flow from F-statistics under isolation by distance.

I reexamine the use of isolation by distance models as a basis for the estimation of demographic parameters from measures of population subdivision. To that aim, I first provide results for values of F-statistics in one-dimensional models and coalescence times in two-dimensional models, and make more precise earlier results for F-statistics in two-dimensional models and coalescence times in one-dimensional models. Based on these results, I propose a method of data analysis involving the regression of FST/(1-FST) estimates for pairs of subpopulations on geographic distance for populations along linear habitats or logarithm of distance for populations in two-dimensional habitats. This regression provides in principle an estimate of the product of population density and second moment of parental axial distance. In two cases where comparison to direct estimates is possible, the method proposed here is more satisfactory than previous indirect methods.

Gene Frequency↗
PubMed1987

Distance versus destination: stream selectivity of elderly interstate migrants.

Migration streams of persons age 60 years and older that share a common origin state, but with widely separated county-group destinations, were examined to determine the relative effect of distance upon migration selectivity. Socioeconomic and demographic characteristics common to selectivity studies were used for the comparisons. The findings showed that distance made little difference. Controlling for destination, we matched and compared the characteristics of older migrants from states of different distances. We looked at those coming to Arizona from California, Illinois, and Ohio, to the New York City suburbs from Pennsylvania and Florida, and to Chicago from Michigan and California. Repeatedly the story was the same. Distance was not an important factor; significant differences between these streams were rare. This analysis used the 1-in-100 1970 census public use microdata sample and used tests for identifying significant differences between streams.

Aged↗
PubMed2000

Allele association studies with SSR and SNP markers at known physical distances within a 1 Mb region embracing the ALDH2 locus in the Japanese, demonstrates linkage disequilibrium extending up to 400 kb.

There has been considerable recent debate concerning the distances over which levels of allelic association useful for genomic quantitative trait locus (QTL) scans can be detected. We have examined simple sequence repeat (SSR) polymorphisms and two single nucleotide polymorphisms (SNPs) in the region flanking the aldehyde dehydrogenase 2 locus, ALDH2, in populations of Japanese alcoholics and controls. These groups differ significantly in the allele frequencies for the functional SNP in exon XII of this gene located on chromosome 12. The results obtained with SSR markers complement recent investigations with SNPs over similar distances at the TCR alpha/delta locus. Significant allelic association with this marker could be detected for SSRs over distances up to 400 kb and over 37 kb for the SNP thereby extending the distance over which LD at this locus could be detected by an order of magnitude. Furthermore, as a proof of principle, we show that comparisons of allele frequency differences for the SSR markers in the case (alcoholics) and control populations would have detected the ALDH2 marker as a putative QTL. Extending the tests to include alleles at two or three flanking loci suggests that the power to detect QTLs through association can be enhanced significantly.

Alcohol Dehydrogenase↗
PubMed2003

The use of fixed distance embryo transfer after IVF/ICSI equalizes the success rates among physicians.

BACKGROUND: It is suggested that the skill of the physician performing the embryo transfer may influence the outcome of the procedure. In this study we investigated the effects of a change in embryo transfer technique on the variability in success rates among physicians. METHODS: Retrospectively 4439 transfer cycles in which two different embryo transfer techniques were applied by seven physicians were studied. In the first 2210 cycles, transfers were performed using the 'clinical touch' method. In the following 2229 cycles, the so-called fixed distance technique was used. RESULTS: With the clinical touch method pregnancy rates differed greatly among providers, whereas after the introduction of the fixed distance technique these differences disappeared. Furthermore, the overall clinical pregnancy rate increased from 33.6 to 40.4% per transfer. Using smoothing spline curves we failed to detect a sudden rise in pregnancy rates at the time the transfer method was changed. CONCLUSIONS: The introduction of the fixed distance technique greatly reduced the variation in pregnancy rates among physicians. The overall increase in pregnancy rates after the introduction is likely to be related to the change in technique although definite proof is difficult. Both observations are suggested to be attributable to the atraumatic character of the fixed distance technique.

Embryo Transfer↗
PubMed2005

The "inverse relationship between evolutionary rate and age of mammalian genes" is an artifact of increased genetic distance with rate of evolution and time of divergence.

It has recently been claimed that older genes tend to evolve more slowly than newer ones (Alba and Castresana 2005). By simulation of genes of equal age, we show that the inverse correlation between age and rate is an artifact caused by our inability to detect homology when evolutionary distances are large. Since evolutionary distance increases with time of divergence and rate of evolution, homologs of fast-evolving genes are frequently undetected in distantly related taxa and are, hence, misclassified as "new." This misclassification causes the mean genetic distance of 'new' genes to be overestimated and the mean genetic distance of "old" genes to be underestimated.

Animals↗
PubMed1997

Sensitivity of NMR internucleotide distances to B-DNA conformation: underlying mechanics.

Nuclear magnetic resonance (NMR) spectroscopy, combining correlated spectroscopy (COSY) coupling constant measurements with nuclear Overhauser effect spectroscopy (NOESY) interatomic distances, should make it possible to determine an averaged solution structure for DNA oligomers. However, even if such data could be obtained with high accuracy, it is not clear which structural parameters of DNA would be determined. Here, the relationships between measurable internucleotide distances and helical parameters are systematically studied through molecular modelling. Investigations are carried out using four representative sequences, (ACGT)n, (TCGA)n, (AGCT)n and (TGCA)n, composed of repeated tetranucleotides belonging to oligomers previously studied by NMR. Correlations between interatomic distances become evident and strong connections between distances and inter-base helical parameters are observed. Results imply that twist, roll, shift and slide values can be accurately determined from NMR data. Sequence independent mechanical coupling which link backbone and sugar conformations to helical twist are also described.

Base Sequence↗
PubMed2002

Efficient biased estimation of evolutionary distances when substitution rates vary across sites.

This paper deals with phylogenetic inference when the variability of substitution rates across sites (VRAS) is modeled by a gamma distribution. We show that underestimating VRAS, which results in underestimates for the evolutionary distances between sequences, usually improves the topological accuracy of phylogenetic tree inference by distance-based methods, especially when the molecular clock holds. We propose a method to estimate the gamma shape parameter value which is most suited for tree topology inference, given the sequences at hand. This method is based on the pairwise evolutionary distances between sequences and allows one to reconstruct the phylogeny of a high number of taxa (>1,000). Simulation results show that the topological accuracy is highly improved when using the gamma shape parameter value given by our method, compared with the true (unknown) value which was used to generate the data. Furthermore, when VRAS is high, the topological accuracy of our distance-based method is better than that of a maximum likelihood approach. Finally, a data set of Maoricicada species sequences is analyzed, which confirms the advantage of our method.

Algorithms↗
PubMed1997

Confidence intervals of evolutionary distances between sequences and comparison with usual approaches including the bootstrap method.

Two methods are commonly employed for evaluating the extent of the uncertainty of evolutionary distances between sequences: either some estimator of the variance of the distance estimator, or the bootstrap method. However, both approaches can be misleading, particularly when the evolutionary distance is small. We propose using another statistical method which does not have the same defect: interval estimation. We show how confidence intervals may be constructed for the Jukes and Cantor (1969) and Kimura two-parameter (1980) estimators. We compare the exact confidence intervals thus obtained with the approximate intervals derived by the two previous methods, using artificial and biological data. The results show that the usual methods clearly underestimate the variability when the substitution rate is low and when sequences are short. Moreover, our analysis suggests that similar results may be expected for other evolutionary distance estimators.

Algorithms↗
PubMed2000

Weighted neighbor joining: a likelihood-based approach to distance-based phylogeny reconstruction.

We introduce a distance-based phylogeny reconstruction method called "weighted neighbor joining," or "Weighbor" for short. As in neighbor joining, two taxa are joined in each iteration; however, the Weighbor criterion for choosing a pair of taxa to join takes into account that errors in distance estimates are exponentially larger for longer distances. The criterion embodies a likelihood function on the distances, which are modeled as correlated Gaussian random variables with different means and variances, computed under a probabilistic model for sequence evolution. The Weighbor criterion consists of two terms, an additivity term and a positivity term, that quantify the implications of joining the pair. The first term evaluates deviations from additivity of the implied external branches, while the second term evaluates confidence that the implied internal branch has a positive branch length. Compared with maximum-likelihood phylogeny reconstruction, Weighbor is much faster, while building trees that are qualitatively and quantitatively similar. Weighbor appears to be relatively immune to the "long branches attract" and "long branch distracts" drawbacks observed with neighbor joining, BIONJ, and parsimony.

Animals↗
PubMed1994

Estimation of genetic distance and coefficient of gene diversity from single-probe multilocus DNA fingerprinting data.

DNA fingerprinting exhibits multilocus genotypes of individuals, detected by the use of a single multilocus probe. Consequently, population data on DNA fingerprinting do not provide a complete characterization of the genetic variation in terms of allele-frequency distributions, since neither the number of loci nor the locus affiliation of alleles is directly observable. Yet DNA fingerprinting has been proved to be a cost-effective method of detecting hypervariable polymorphisms in several organisms, where the traditional loci fail to detect enough variation for microevolutionary studies. In the present paper we demonstrate that the above-mentioned features of DNA fingerprinting data do not cause any serious problem when they are used in evolutionary studies. Bias-corrected estimators of Nei's standard and minimum genetic distances are derived, and, by an application of this theory to data on seven short tandem repeat loci in three major human populations, it is shown that these modified measures of genetic distances based on DNA fingerprint patterns are quite close to Nei's distances based on locus-specific allele frequencies. Empirical as well as theoretical support of the adequacy of such genetic distances from DNA fingerprinting data is also discussed, and it indicates that the technical limitations of DNA fingerprinting should not deter the use of the method for short-term evolutionary studies.

Alleles↗
PubMed1988

Relative efficiencies of the maximum parsimony and distance-matrix methods in obtaining the correct phylogenetic tree.

The relative efficiencies of the maximum parsimony (MP) and distance-matrix methods in obtaining the correct tree (topology) were studied by using computer simulation. The distance-matrix methods examined are the neighbor-joining, distance-Wagner, Tateno et al. modified Farris, Faith, and Li methods. In the computer simulation, six or eight DNA sequences were assumed to evolve following a given model tree, and the evolutionary changes of the sequences were followed. Both constant and varying rates of nucleotide substitution were considered. From the sequences thus obtained, phylogenetic trees were constructed using the six tree-making methods and compared with the model (true) tree. This process was repeated 300 times for each different set of parameters. The results obtained indicate that when the number of nucleotide substitutions per site is small and a relatively small number of nucleotides are used, the probability of obtaining the correct topology (P1) is generally lower in the MP method than in the distance-matrix methods. The P1 value for the MP method increases with increasing number of nucleotides but is still generally lower than the value for the NJ or DW method. Essentially the same conclusion was obtained whether or not the rate of nucleotide substitution was constant or whether or not a transition bias in nucleotide substitution existed. The relatively poor performance of the MP method for these cases is due to the fact that information from singular sites is not used in this method. The MP method also showed a relatively low P1 value when the model of varying rate of nucleotide substitution was used and the number of substitutions per site was large. However, the MP method often produced cases in which the correct tree was one of several equally parsimonious trees. When these cases were included in the class of "success," the MP method performed better than the other methods, provided that the number of nucleotide substitutions per site was small.

Biological Evolution↗
PubMed2006

Effects of travel distance and the season of the year on death rates of broilers transported to poultry processing plants.

Death losses among broilers transported to processing plants are caused by poor welfare. The number of birds dying during transport and in processing plants shortly after arrival there may serve as an indicator of the quality of welfare during loading and transport. In the Czech Republic, shipments of broilers to processing plants were monitored from 1997 to 2004. It was found that the mortality of broilers during transport was 0.247%, but it varied according to the transport distance to the processing plant from 0.146% (50 km maximum) to 0.862% (>300 km). The broiler mortality in transit was also influenced by the season of the year. The highest mortality was found in summer months, especially in June, July, and August, and in winter months, especially in December, January, and February. A comparison between period 1 (1997 to 2000) and period 2 (2001 to 2004) showed a long-term adverse trend in the number of broilers dying during transport to processing plants for all of the distances monitored (except transport distances <50 km), because the overall number of dead birds on arrival to processing plants increased from 0.224 to 0.265% (index of 1.18). This difference is statistically significant (P = 0.000). The stress caused to broilers by transport to processing plants is reflected in higher transport-related mortality of the birds. Long-term trends point to an increase in death losses of broilers. Longer transport distances and transportation in summer and winter months have led to an increase in death losses among broilers transported to processing plants.

Abattoirs↗
PubMed1981

Reproducing movement in the lower extremity using kinesthetic cues of distance and location.

The purpose of this study was to determine if kinesthetic cues of distance or location serve as references in motor memory for reproducing movement in the lower extremity. Thirty normal subjects randomly reproduced criterion movements of 30, 60, and 90 degrees of knee flexion. Starting positions of the criterion and reproduction movements were varied. Reproducing distance required that subjects move the same amplitude as the criterion movement, while reproducing location involved moving to the end position of the criterion movement. Results showed that reproductions based on location were significantly (p less than .05) more accurate than those based on distance cues. Reproductions of 30 and 60 degrees were found to be significantly (p less than .05) less variable than 90-degree reproduction movements. The results were explained according to the theories that have been proposed for retention of kinesthetic distance and location cues in motor memory.

Adult↗
PubMed1984

Difference between in vivo and postmortem distances between anterior chest and heart surface. A combined autopsy and in vivo computerized tomography study.

The distance between anterior chest surface and intrapericardial surfaces of the heart and great blood vessels was measured on 37 cases (seven with acute fatal hemopericardium) at autopsy and on 24 live persons by computerized tomography. At autopsy, the apex of the heart was always closest to the skin surface except in cases with acute fatal hemopericardium, where the heart was displaced backwards by 10-40 mm. At computerized tomography, chest-heart distances were approximately 16 mm shorter than at autopsy. Changing the position of the patient from supine to prone decreased the distances by about 10 mm. The data presented demonstrate that the topography of the heart and great vessels is changing with the position of the body in vivo and that chest-heart distance tend to increase postmortem; therefore, the depth of a stab wound in the anterior surface of the heart as measured at autopsy should be regarded as a maximal estimate of the length of the stabbing weapon actually having penetrated the tissues.

Adolescent↗
PubMed1998

Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance running: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether homeopathic Arnica 30X can reduce muscle soreness following long-distance running more than a placebo. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Long-distance runs taking place in the community. SUBJECTS: A total of 519 runners anticipating delayed-onset muscles soreness after long-distance races. INTERVENTIONS: A homeopathic medicine (Arnica 30x) and an indistinguishable placebo. OUTCOME MEASURES: Subjects completed a visual analog scale and Likert scale of muscle soreness every morning and evening for the 5 days following their race. Race time was also recorded. The main outcome measure was mean 2-day visual analog scores. RESULTS: Results were obtained from 400 subjects. Groups were well matched at baseline. Mean 2-day visual analog soreness scores for Arnica and placebo were 45.2 mm and 41.0 mm, respectively. The 95% confidence interval was between 8.81 mm in favor of placebo and 0.51 mm in favor of Arnica. No differences were found for Likert scores or race time. CONCLUSION: Homeopathic Arnica 30x is ineffective for muscle soreness following long-distance running.

Adult↗